The objective of this project is to study the permeability of the peritubular capillaries in the kidney to macromolecules (albumin, beta lipoproteins and dextran) in experimental diabetic vascular disease. One of the most common and life-threatening complications of chronic diabetes mellitus is microangiopathy, the thickening, hardening and occlusion of the small blood vessels. This investigation is aimed at studying (1) the development in time of functional alterations in macromolecular permeability of the capillary wall, in parallel with the morphological state of the capillaries, (2) The conditions that accelerate and retard these functional alterations, (3) and isolating the factors that may be responsible for microangiopathy in diabetes. In these studies, a screening test is applied to experimental diabetic animals and their matched pair controls every four weeks to ascertain whether any alteration has occurred in their capillary permeability to albumin. In these animals more extensive testing is also carried out to determine the kinetics of passage of macromolecules from plasma to lymph. The significance of this study is underlined by the fact that the death of the chronic diabetic patient occurs most frequently because of microvascular disease of the kidneys and the heart.